Effects of combined administration of alfacalcidol and risedronate on cancellous and cortical bone mass of the tibia in glucocorticoid-treated young rats.
The purpose of the present study was to examine the effects of combined administration of alfacalcidol (ALF) and risedronate (RIS) on cancellous and cortical bone mass of the tibia in glucocorticoid (GC)-treated young rats. One hundred and nine female Sprague-Dawley rats, 3 months of age, were randomly divided by the stratified weight method into eleven groups according to the following treatment schedule: baseline control, a 4-week age-matched control, and a 4-week GC administration with a 4-week concomitant administration of vehicle, ALF, RIS, or ALF+RIS, and an 8-week age-matched control and 8-week GC administration with a 4-week administration of vehicle, ALF, RIS, or ALF+RIS that was initiated after a 4-week administration of GC. The GC (methylprednisolone sodium succinate, 5.0 mg/kg) and RIS (10 microg/kg) were administered subcutaneously 3 times a week. ALF (0.08 microg/kg) was administered orally 5 times a week. At the end of the experiment, static and dynamic bone histomorphometric analyses were performed on cancellous bone of the proximal tibial metaphysis and cortical bone of the tibial diaphysis. A 4-week GC administration induced a loss of cancellous bone volume/total tissue volume (BV/TV) compared with the age-matched control as a result of decreased bone formation and increased bone erosion, while an 8-week GC administration induced both losses of cancellous BV/TV and of percent cortical area (Ct Ar) compared with the age-matched control as a result of decreased trabecular bone formation and increased trabecular and endocortical bone erosion. ALF prevented the loss of cancellous BV/TV at the 4th week by mildly suppressing bone erosion without reducing bone formation, and it restored cancellous BV/TV and increased percentage of Ct Ar at the 8th week by preventing a reduction in trabecular bone formation and mildly suppressing trabecular bone erosion and by strongly suppressing endocortical bone erosion, respectively. RIS restored only cancellous BV/TV at 8 weeks by strongly suppressing bone formation and bone erosion. Combined administration of ALF and RIS increased total tissue area of cortical bone at the 4th and 8th weeks by markedly increasing periosteal bone formation. The present study showed the efficacy of combined administration of ALF and RIS for the geometry of cortical bone in GC-treated rats.
Iwamoto
Jun
J
Department of Sports Medicine, Keio University School of Medicine, Tokyo, Japan. jiwamoto@sc.itc.keio.ac.jp
Seki
Azusa
A
Takeda
Tsuyoshi
T
Yamada
Harumoto
H
Sato
Yoshihiro
Y
Yeh
James K
JK
D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000494:pharmacology; D006887:Hydroxycholecalciferols / Q000494:pharmacology* / Q000627:therapeutic use; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology; D010024:Osteoporosis / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D013977:Tibia / Q000187:drug effects* / Q000502:physiology
D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D006887:Hydroxycholecalciferols; D000068296:Risedronic Acid; D012968:Etidronic Acid; C008088:alfacalcidol